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The role of peroxisomal function on the prevention of obesity and glucose intolerance

Grant number: 10/20322-4
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): May 01, 2011
Effective date (End): December 31, 2013
Field of knowledge:Biological Sciences - Biochemistry - Metabolism and Bioenergetics
Principal Investigator:Rui Curi
Grantee:Jarlei Fiamoncini
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:10/02963-2 - Modulation of inflammation and insulin resistance by omega-3 fatty acids and palmitoleate, AP.TEM
Associated scholarship(s):11/21618-7 - Involvement of acetate and bile acids on the prevention of glucose intolerance mediated by n-3 fatty acids, BE.EP.PD

Abstract

Obesity and diabetes are reaching epidemic proportions and high plasma concentrations of saturated fatty acids (FA) are associated with these diseases. Saturated FA can induce insulin resistance, opposing the effects of n-3 polyunsaturated FA (n-3 PUFA), which are involved on the prevention of this condition. The activation of the peroxisome proliferator activated receptor (PPAR) and increased peroxisomal ²-oxidation of FA are among the mechanisms to explain the beneficial effects of n-3 PUFA. This project is based on the hypothesis that other than contributing to FA oxidation, peroxisome proliferation also leads to increased bile acid synthesis. If confirmed, this mechanism would be a way for wasting the excessive fat ingested through bile acid excretion, without requiring complete FA oxidation to CO2, preventing the accumulation of triacylglycerols in adipose tissue and other organs. In order to test this theory, we are planning to feed C57/Bl6 mice with hyperlipidic diets containing high and low concentrations of n-3 PUFA as well as treat the mice with PPAR agonists and antagonists. Considering the importance of peroxisomes in liver, detailed studies of lipid metabolism in this organ are going to be undertaken using primary hepatocytes and a cell line (HepG2) culture. The results of this study will add to the knowledge on lipid metabolism and the aetiology of diabetes and obesity.